桂东南地区2型糖尿病肾病与 MTHFR 基因 C677T 多态性的相关性

目的：研究亚甲基四氢叶酸还原酶（MTHFR）基因多态性与2型糖尿病肾病（DN）的关系。方法应用聚合酶链反应-限制性片段长度多态性的方法,检测桂东南地区2型糖尿病患者163例 MTHFR 基因 C677T 多态性,其中 DN 82例、单纯糖尿病（DM）81例和健康对照组（CON）77例。同时检测血清同型半胱氨酸（Hcy）水平,并比较各组间 MTHFR 基因型频率、等位基因频率和 Hcy 水平。结果DN 组 MTHFR 基因纯合基因型（TT）、杂合基因型（CT）及 T 等位基因频率（分别为4．9％、37．8％和23．8％）均明显高于 DM 组（分别为2．5％、28．4％和16．7％）和 CON 组（分别为0．0％、29．8％和14．9％）,基因型和等位基因频率分布差异均有统计学意义（P ＜0．05）,而 DM 组和 CON 组之间的分布差异无统计学意义（P ＞0．05）。单因素 Logistic 回归分析结果显示,MTHFR 基因型 C677T 多态性与 DN 的发生密切相关（OR 值及其95％CI 分别为1．660、1．038和2．655）。携带T 等位基因患者血中 Hcy 水平显著高于未携带 T 等位基因患者,差异有统计学意义（P ＜0．01）。结论MTHFR 基因 C677T 多态性与桂东南地区2型糖尿病患者 DN 相关,MTHFR T 等位基因可能是该地区 DN 的易感基因。     

MTHFR基因多态性与脊髓亚急性联合变性的相关性分析

目的　探讨5,10- 亚甲基四氢叶酸还原酶（MTHFR）基因C677T 位点和A1298C 位点多态性与脊髓亚急性联合变性（SCD）的关系。方法 选择2017 年1 月～ 2020 年7 月于宝鸡市中心医院神经内科诊治的85 例SCD 患者作为病例组,另外募集100 例健康体检者作为对照组。采用荧光定量PCR 法检测MTHFR 基因C677T和A1298C 位点多态性,比较各组两位点基因型和等位基因频率,分析两位点多态性与SCD 发病的相关性。结果　病例组C677T 位点TT 基因型和T 等位基因频率均高于对照组（χ2=10.527,11.144,均P ＜ 0.05）,A1298C 位点CC 基因型和C 等位基因频率均高于对照组（χ2=6.575,6.076,均P ＜ 0.05）,差异均有统计学意义。C677T位点和A1298C 位点基因多态性均与同型半胱氨酸水平增高密切相关（χ2=19.625,10.786,均P ＜ 0.05）;与血清VitB12 和叶酸水平均无明确相关性（χ2=1.827~5.549,均P ＞ 0.05）。多因素分析示携带C677T 位点TT 基因型是SCD 发病的独立危险因素（OR=2.768,95% CI:1.487~5.516,P=0.005）,A1298C 位点基因多态性与SCD发病无明确相关性（OR=2.190,95% CI:0.958~5.004,P=0.067）。结论　MTHFR 基因C677T 位点突变与SCD发病密切相关。     

MTHFR C677T位点基因多态性与高同型半胱氨酸血症及急性冠状动脉综合征的关系

目的探讨亚甲基四氢叶酸还原酶(MTHFR)C677T基因多态性与高同型半胱氨酸血症(HHcy)及急性冠状动脉综合征(ACS)的关系。方法采用聚合酶链反应(PCR)-芯片杂交法检测81例ACS患者[同型半胱氨酸(Hcy)正常患者51例、合并HHcy患者30例]及98名体检健康者(正常对照组)MTHFR C677T位点基因多态性,并分析其与HHcy及ACS发病易感性的关联。结果 ACS组和正常对照组基因型分布均符合Hardy-Weinberg遗传平衡原则。相对于正常对照组,MTHFR C677T位点TT基因型相对于CC基因型、TT基因型相对于CT+CC基因型、T等位基因相对于C等位基因,其发生ACS的OR值(95%CI)分别为2.60(1.12~6.03)、2.02(1.06~3.86)和1.66(1.09~2.53)。在ACS患者中,MTHFR C677T位点TT基因型相对于CT+CC基因型,发生HHcy的OR值(95%CI)为2.74(1.08~7.00)。结论 MTHFR C677T位点TT基因型是HHcy的危险因子,可增加ACS的发病风险。     

MTHFR基因多态性和同型半胱氨酸在冠心病脑梗死和糖尿病中的分析

目的探讨冠心病、脑梗死、糖尿病患者亚甲基四氢叶酸还原酶（MTHFR）和血浆同型半胱氨酸（Hcy）的关系,对三个病种的MTHFR基因型进行分析。方法收集120例冠心病,214例脑梗死,112例糖尿病患者及98例健康体检者标本,采用聚合酶链式反应-限制性片段长度多态性（PCR-RFLP）技术检测MTHFRC677T基因,采用酶循环法检测血浆Hcy,比较四组MTHFRC677T基因多态性及血浆Hcy的差异。结果（1）MTHFR基因型在冠心病,脑梗死和糖尿病组与健康对照组间差异无统计学意义（P＝0．670）;（2）MTHFR基因频率在冠心病,脑梗死和糖尿病组与健康对照组间差异无统计学意义（P＝0．721）;（3）冠心病组和脑梗死组的MTHFR基因TT型患者的Hcy水平远远高于CC型和CT型患者（F＝6．212,P＝0．003;F＝44． 362,P＝0．000）。结论不同病种间MTHFR基因型和基因频率差异无统计学意义,但冠心病组和脑梗死组MTHFR基因TT型患者Hcy水平则远远高于CC型和CT型患者,差异有统计学意义。     

青年缺血性脑血管疾病独立危险因子与N5及N10-亚甲基四氢叶酸还原酶基因突变的关系

背景：血浆同型半胱氨酸浓度升高是动脉粥样硬化性血栓性脑梗死的独立危险因素，同型半胱氨酸在转硫化和再甲基化过程中的代谢酶Ns，N10-亚甲基四氢叶酸还原酶（methylene tetrahydrofolate reduetase，MTHFR）基因突变可致血浆同型半胱氨酸浓度升高。 目的：探讨同型半胱氨酸血症、同型半胱氨酸代谢关键酶MTHFR基因突变与青年缺血性脑血管疾病的关系。 设计：病例-对照观察。 单位：吉林大学中丑联谊医院神经内科。 对象：于2003-04／2004-12吉林大学中丑联谊医院神经内科收治发病2d内住院的青年脑梗死患者100例，为病例组，男73例，女27例；年龄27-45岁，平均（42&;#177;5）岁。对照组100例为同期健康体检者：男70例，女30例；年龄18～45岁，平均（39&;#177;4）岁。 方法：以高效液相色谱法测定受试者空腹血浆同型半胱氨酸，采用聚合酶链反应-限制性内切酶片段长度多态性分析和扩增阻滞突变体系法，对MTHFR基因C677T位点和A1298C位点进行检测。 主要观察指标：MTHFRC677T和A1298C基因检测，血浆同型半胱氨酸浓度与MTHFR基因型的关系。 结果：纳入患者100例和正常对照100例，均进入结果分析。④MTHFRC677T和A1298C基因检测：MTHFR C677T基因检测病例组和对照组基因型分布、纯合子频率和等位基因频率差异均显著（P〈0．01）。而MTHFR A1298C基因检测病例组和对照组基因型分布、纯合子频率和等位基因频率差异均无显著性（P〉0．05）。②血浆同型半胱氨酸浓度与MTHFR基因型的关系：MTHFR C677T和A1298C各基因型问血浆同型半胱氨酸浓度差异有显著性（P〈0．001）。2个位点突变结果LSD-t检验显示纯合子与杂合子，纯合子与野生型血浆同型半胱氨酸浓度均数差有统计学意义（P〈0．05）。MTHFR C677T和A1298C杂合子与野生型血浆同型半胱氨酸浓度均数差无统计学意义（P〉0．05）。 结论：MTHFR C677T和A1298C突变均导致血浆同型半胱氨酸浓度明显增高。MTHFR C677T多态性位点是青年缺血性脑血管疾病的独立危险因子。MTHFR A1298C基因突变与青年缺血性脑血管疾病发病无相关性。     

MTHFR C677T/MS A2756G基因多态性及血浆Hcy水平与阿尔茨海默病的关系

目的:探讨亚甲基四氢叶酸还原酶(MTHFR) C677T、蛋氨酸合成酶(MS) A2756G基因多态性及血浆同型半胱氨酸(Hcy)水平与阿尔茨海默病(AD)的关系.方法:用多聚酶链反应技术分析75例AD患者(AD组)及71例健康老人(对照组)的MTHFR C677T、MS A2756G基因多态性及测定血浆Hcy、叶酸和VitB12水平.结果:(1)两组MTHFR C677T、MS A2756G的基因型频率及等位基因频率分布差异无统计学意义(P＞0.05);(2)对照组携带MTHFR T等位基因者血浆Hcv水平升高(P＜0.05);两组血浆Hcy水平与MS基因A2756G基因型不相关(P＞0.05) 结论:MTHFR基因C677T及MS基因A2756G多态性与AD发生不相关,AD患者血浆Hcy水平升高可能主要与体内叶酸、VitB12不足有关     

亚甲基四氢叶酸还原酶(MTHFR)C677T基因多态性与血压变化的相关性研究

高血压和高同型半胱氨酸血症是冠状动脉粥样硬化性心脏病(简称冠心病CVD)的独立危险因素。同型半胱氨酸浓度主要受亚甲基四氢叶酸还原酶(MTHFR)C677T基因多态性的影响,尤其受纯合子(即TT基因型)的影响。本综述旨在研究MTHFR C677T基因多态性与血压变化的关系。     

新疆维汉民族亚甲基四氢叶酸还原酶基因多态性及血浆同型半胱氨酸与冠状动脉粥样硬化性心脏病的关系

目的:分析新疆维汉民族亚甲基四氢叶酸还原酶基因C677T多态性及其与同型半胱氨酸水平、冠状动脉粥样硬化性心脏病之间的关系,以期为冠心病的预防和优化康复治疗提供理论依据。方法:收集2004-09/2005-10在新疆医科大学第一附属医院心内科住院并行冠状动脉造影术的320例维汉民族患者,按冠状动脉造影结果分为冠状动脉粥样硬化性心脏病组(n=189)与对照组(n=131),应用聚合酶链反应-限制性内切酶长度多态性方法检测亚甲基四氢叶酸还原酶基因C677T多态性,用荧光偏振免疫分析法测定血浆同型半胱氨酸水平,并分析同型半胱氨酸及亚甲基四氢叶酸还原酶基因C677T多态性与冠心病的关联性。结果:320例全部进入结果分析。①维汉民族冠状动脉粥样硬化性心脏病组和对照组亚甲基四氢叶酸还原酶C677TCC、CT、TT3种基因型分布(维吾尔族,χ2=9.561,P=0.008;汉族,χ2=10.618,P=0.005)和等位基因频率分布(维吾尔族,χ2=4.857,P=0.028;汉族,χ2=5.158,P=0.023)差异有统计学意义;但冠状动脉粥样硬化性心脏病组和对照组内维汉不同民族基因型分布和等位基因频率分布差异无统计学意义(P>0.05)。②维汉民族冠状动脉粥样硬化性心脏病组和对照组中,亚甲基四氢叶酸还原酶C677T各基因型之间血浆同型半胱氨酸水平的差异均有统计学意义(P<0.05)。其中TT基因型的血浆同型半胱氨酸水平均高于同组同民族CT和CC型者;CT基因型与CC基因型之间血浆同型半胱氨酸水平的差异无统计学意义P>0.05)。③经多因素非条件Logistic回归分析显示,亚甲基四氢叶酸还原酶C677T基因突变(OR=1.478)、同型半胱氨酸(OR=1.057)等因素是冠状动脉粥样硬化性心脏病的危险因素。结论:①同型半胱氨酸代谢关键酶基因亚甲基四氢叶酸还原酶C677T存在多态性,无民族差异。②亚甲基四氢叶酸还原酶C677T可导致血浆同型半胱氨酸明显增高。③亚甲基四氢叶酸还原酶C677T多态性和同型半胱氨酸是新疆维汉民族冠状动脉粥样硬化性心脏病发病的独立危险因素。     

MTHFR C677T基因多态性与叶酸治疗急性脑梗死伴高同型半胱氨酸血症疗效的相关性研究

目的:探讨亚甲基四氢叶酸还原酶(MTHFR)C677T基因多态性与叶酸干预治疗急性脑梗死伴高同型半胱氨酸(Hcy)血症疗效的相关性。方法:选取107例急性脑梗死伴高Hcy血症患者为脑梗死伴高Hcy组,32例急性脑梗死无高Hcy血症患者为脑梗死无高Hcy组,42例健康志愿者为健康对照组,比较3组血浆中Hcy水平、MTHFR C677T基因多态性及叶酸治疗急性脑梗死复发情况,分析MTHFR C677T基因多态性与叶酸治疗急性脑梗死伴高Hcy血症疗效的相关性。结果:与健康对照组比较,脑梗死伴高Hcy组MTHFR C677T位点TT基因型比例明显增高(P<0.05)。MTHFR C677T位点TT基因型相对于CT+CC基因型发生高Hcy血症的OR值为2.94(1.37～5.45),差异有统计学意义(P<0.05)。TT基因型患者脑梗死复发率较高(26.3%)。结论:叶酸干预治疗急性脑梗死伴高Hcy患者携带MTHFR C677T位点TT基因型时,脑梗死复发率增加。     

湖南地区冠心病患者MTHFR C677T基因多态性与血浆同型半胱氨酸及血脂水平关系的研究

目的分析湖南地区中老年冠心病患者亚甲基四氢叶酸还原酶(MTHFR)C677T基因多态性与血浆同型半胱氨酸(Hcy)及血脂水平的相关性,为该地区研究冠心病病因、发病机制及诊断提供参考。方法以该院351例初诊为冠心病的患者为研究对象,并设置健康对照组147例,分别检测各组血浆Hcy及血脂水平,并采用PCR-金磁微粒层析法测定MTHFR C677T基因型,统计分析冠心病患者MTHFR C677T基因型及各基因型与血浆Hcy及血脂水平的相关性。结果冠心病组的血浆Hcy水平,MTHFR C677T基因CC、CT、TT三种基因型频率和C、T两种等位基因频率与健康对照组相比,差异有统计学意义(P0.05);冠心病组TT型、CT型血浆Hcy水平高于CC型,健康对照组的TT型血浆Hcy水平明显高于CT、CC型,差异有统计学意义(P0.05)。结论 MTHFR C677T基因多态性是冠心病发病的危险因素,与血浆Hcy水平密切相关,TT型纯合突变和T等位基因使Hcy水平显著升高,而血脂水平与MTHFR C677T基因多态性无明显相关性。因此,血浆Hcy水平及MTHFR C677T多态性可以作为该地区研究冠心病病因、发病机制及其遗传机制的重要参考指标。     

Determination of creatine kinase isoenzyme MB activity in serum using immunological inhibition of creatine kinase M subunit activity. Activity kinetics and diagnostic significance in myocardial infarction.

This is a new method for the determination of creatine kinase isoenzyme MB activity in serum. The method uses direct activity measurement of creatine kinase B subunit activity after blocking of CK-M subunit activity by inhibiting antibodies. The test takes no longer than 15 min. The method yields an intra-serial C.V. of 2.0-12.9%, and a C.V. from day to day of 5.5%. The detection limit is 3.4 U/l creatine kinase MB. In the 95 cases with proven myocardial infarction several types of creatine kinase MB activity kinetics could be determined. The percentage of creatine kinase MB of peak CK-total is 6-25%, with a mean of 11.1%. The amount of creatine kinase MB with respect to total CK activity after reinfarction is higher than the amount after initial infarction.     

Dissociable correlates of two classes of retrieval processing in prefrontal cortex

Although substantial evidence suggests that the prefrontal cortex (PFC) implements processes that are critical for accurate episodic memory judgments, the specific roles of different PFC subregions remain unclear. Here, we used event-related functional magnetic resonance imaging to distinguish between prefrontal activity related to operations that (1) influence processing of retrieval cues based on current task demands, or (2) are involved in monitoring the outputs of retrieval. Fourteen participants studied auditory words spoken by a male or female speaker and completed memory tests in which the stimuli were unstudied foil words and studied words spoken by either the same speaker at study, or the alternate speaker. On "general" test trials, participants were to determine whether each word was studied, regardless of the voice of the speaker, whereas on "specific" test trials, participants were to additionally distinguish between studied words that were spoken in the same voice or a different voice at study. Thus, on specific test trials, participants were explicitly required to attend to voice information in order to evaluate each test item. Anterior (right BA 10), dorsolateral prefrontal (right BA 46), and inferior frontal (bilateral BA 47/12) regions were more active during specific than during general trials. Activation in anterior and dorsolateral PFC was enhanced during specific test trials even in response to unstudied items, suggesting that activation in these regions was related to the differential processing of retrieval cues in the two tasks. In contrast, differences between specific and general test trials in inferior frontal regions (bilateral BA 47/12) were seen only for studied items, suggesting a role for these regions in post-retrieval monitoring processes. Results from this study are consistent with the idea that different PFC subregions implement distinct, but complementary processes that collectively support accurate episodic memory judgments.     

俯卧位通气对高海拔地区肺复张治疗无效急性呼吸窘迫综合征患者氧合的影响

目的 探讨俯卧位通气对高海拔地区肺复张术(RM)治疗无效急性呼吸窘迫综合征(ARDS)患者的治疗作用.方法 从海拔2260m的地区医院筛选RM治疗无效的41例ARDS患者[平均氧合指数( PaO2/FiO2)较RM前升高＜20％视为RM无效],依不同病因分为肺内源性ARDS组(ARDSp组)和肺外源性ARDS组(ARDSexp组),每组再按信封法随机分为俯卧位组和仰卧位组,即ARDSp俯卧位组(11例)、ARDSp仰卧位组(9例)、ARDSexp俯卧位组(10例)、ARDSexp仰卧位组(11例).在通气前及通气1、2、3、4h监测动脉血氧分压( PaO2)、PaO2/FiO2、静态顺应性(Cst)、气道阻力(Raw)的变化.结果 通气lh时,ARDSexp俯卧位组PaO2/FiO2( mm Hg,l mm Hg=0.133 kPa)即较通气前显著升高(157.4±40.6比129.3±48.7,P＜0.05),并随通气时间延长呈持续增高趋势,4h达峰值(219.1 ±41.1);且ARDSexp俯卧位组通气3h内PaO2/FiO2较其他3组显著增高,另3组间则差异无统计学意义.ARDSp俯卧位组、ARDSexp俯卧位组通气4h时PaO2/FiO2均较相应仰卧位组显著增高(208.8±39.7比127.4±47.1,219.1±41.1比124.9±50.8,均P＜0.05).4组通气前后Cst无显著改变,各组间差异也无统计学意义.ARDSp俯卧位组通气4h时Raw(cmH2O·L-1·s-1)较通气前显著降低(6.8±1.7比10.7±1.8,P＜0.05),且明显低于其他3组;其他3组各时间点Raw组内及组间比较差异均无统计学意义.结论 俯卧位通气作为ARDS机械通气重要策略之一,可以改善RM无效高原ARDS患者的氧合,为抢救患者赢得宝贵的时间.     

Digital imaging among medical facilities

The Department of Veterans Affairs (VA) in the USA operates a network of 172 medical centres which all utilize a hospital information system (HIS) which has been developed and is currently maintained by the VA. During the past several years, an image management and communication module has been developed, installed and clinically utilized at the Washington DC and Maryland VA Medical Centres. This image management and communication system, referred to as the decentralized hospital computer program (DHCP) imaging system, is fully integrated with a commercial picture archiving and communication system (PACS). The system is utilized to capture, archive, and display all images generated within the hospital including radiology, nuclear medicine, pathology, endoscopy, bronchoscopy, and dermatology, intraoperative photographs, ECG data, and a limited number of paper documents. The ultimate goal of the project is to have all patient text and image data available at any clinical workstation to any authorized user anywhere within the network of medical centres. Clinical requirements for an imaging workstation include ease of use, rapid and reliable access to the complete set of patient information, and images which are of acceptable quality to meet the requirements of the user and the subspecialty. Patient confidentiality and data security must be safeguarded at all times. Integration of the images with the remainder of the patient's database was found to be critical to the success of the project. The experience at the Washington and Maryland facilities suggests that an imaging system that is successfully integrated with a hospital information system can provide substantial clinical and economic benefits both within and among medical centres. Clinical acceptance and utilization of the system has been excellent, particularly in diagnostic radiology where DHCP Imaging has been interfaced to a commercial PAC system. Based upon this initial experience, the VA has begun to deploy the system throughout its large network of medical centres.     

Myocardial elastography at both high temporal and spatial resolution for the detection of infarcts

Myocardial elastography is a novel method for noninvasively assessing regional myocardial function, with the advantages of high spatial and temporal resolution and high signal-to-noise ratio (SNR). In this paper, in-vivo experiments were performed in anesthetized normal and infarcted mice (one day after left anterior descending coronary artery [LAD] ligation) using a high-resolution (30 MHz) ultrasound system (Vevo 770, VisualSonics Inc., Toronto, ON, Canada). Radiofrequency (RF) signals of the left ventricle (LV) in longitudinal (long-axis) view and the associated electrocardiogram (ECG) were simultaneously acquired. Using a retrospective ECG gating technique, 2-D full field-of-view RF frames were acquired at an extremely high frame rate (8 kHz) that resulted in high-quality incremental displacement and strain estimation of the myocardium. The incremental results were further accumulated to obtain the cumulative displacements and strains. Two-dimensional and M-mode displacement images and strain images (elastograms), as well as displacement and strain profiles as a function of time, were compared between normal and infarcted mice. Incremental results clearly depicted cardiac events including LV contraction, LV relaxation and isovolumetric phases in both normal and infarcted mice, and also evidently indicated reduced motion and deformation in the infarcted myocardium. The elastograms indicated that the infarcted regions underwent thinning during systole rather than thickening, as in the normal case. The cumulative elastograms were found to have higher elastographic SNR (SNR(e)) than the incremental elastograms (e.g., 10.6 vs. 4.7 in a normal myocardium, and 6.0 vs. 2.4 in an infarcted myocardium). Finally, preliminary statistical results from nine normal (m = 9) and seven infarcted (n = 7) mice indicated the capability of the cumulative strain in differentiating infracted from normal myocardia. In conclusion, myocardial elastography could provide regional strain information at simultaneously high temporal (>/=0.125 ms) and spatial ( approximately 55 microm) resolution as well as high precision ( approximately 0.05 microm displacement). This technique was thus capable of accurately characterizing normal myocardial function throughout an entire cardiac cycle, at the same high resolution, and detecting and localizing myocardial infarction in vivo.     

Clinical Pharmacokinetics of Morphine

Morphine, the most widely used mu-opioid analgesic for acute and chronic pain, is the standard against which new analgesics are measured. A thorough understanding of the pharmacokinetics of morphine is required in order to safely and effectively use this analgesic in a wide variety of patients with different levels of organ function. A MEDLINE search was conducted to identify literature published between 1966 and January 2002 relevant to the pharmacokinetics of morphine. These publications were reviewed and the literature summarized regarding unique and clinically important elements of morphine disposition relative to its parenteral administration (including intravenous, intramuscular, subcutaneous, epidural and intrathecal administration), absorption profile (immediate release, controlled release, and sublingual/buccal, and rectal administration), distribution, and its metabolism/ excretion. Special populations, including infants, elderly, and those with renal/liver failure, have a unique morphine pharmacokinetic profile that must be taken into account in order to maximize analgesic efficacy and reduce the risk of adverse events.